Coccidioidomycosis is a recognized opportunistic infection among persons infected with human immunodeficiency virus (HIV). Early in the HIV epidemic, most cases presented as overwhelming diffuse pulmonary disease with a high mortality rate. Although these cases are still seen, patients without significant immunodeficiency frequently present with a community-acquired pneumonia syndrome. Diagnosis can be established by cytological staining, culture, or serologic testing. All patients with HIV infection and symptomatic coccidioidomycosis should be treated with antifungal therapy. Severe cases frequently require a combination of therapy with amphotericin B and a triazole antifungal. Therapy for at least 1 year is recommended, but for patients with a focal pulmonary infection and peripheral blood CD4 lymphocyte counts of >250 cells/microL, it may be reasonable to stop therapy after this time. Other manifestations of coccidioidomycosis require prolonged therapy, and life-long treatment is recommended for persons with meningitis.